Paclitaxel is an anticancer compound primarily derived from the bark of the Taxus brevifolia (Pacific yew) tree. In the 1960's, the National Cancer Institute began a study of plant extracts exhibiting anti-cancer or anti-neoplastic activities. The crude extract of bark from the Taxus brevifolia was found to inhibit a variety of tumors. In 1971, paclitaxel was isolated and described by M. C. Wani et al. (J. Am. Chem. Soc. 93, 2325, (1971)), who defined the structure of paclitaxel using chemical methods and X-ray crystallographic analysis. In 1979, Schiff and coworkers demonstrated paclitaxel's novel mechanism of action. This mechanism includes binding to microtubules and preventing their depolymerization under conditions where depolymerization would normally occur. Paclitaxel is currently used in the treatment of ovarian, breast and non-small cell lung cancers.
Although Paclitaxel is a natural product primarily extracted from the bark of the Pacific yew (T. brevifolia), it is also found in other members of the Taxaceae family including T. canadensis and T. yunnanensis. Paclitaxel is also present in the epigeal parts and roots of other yew species, including the European yew (T. baccata), whose needles contain paclitaxel and analogs, Asian yews (T. wallichiana and T. chinensis), and yew trees cultivated for ornamental purposes. The following varieties of Taxus cultivars have also been found to contain paclitaxel: T.x media “Henryi,” T.x media “Runyan,” T. cuspidata, T.x media “Halloran,” T.x media “Hatfield,” T.x media “Hicksii,” T.x media “Tauntonii,” T.x media “Dark Green Spreader,” T.x media “Wardii,” T.x media “Brownii,” T.x media “Densiformis,” T.x media “Nigra,” T.x cuspidata “Brevifolia,” and T. cuspidata “Spreader.”
All of these species contain paclitaxel in very limited amounts. For example, the bark of T. brevifolia and T. yunnanensis trees contains about 0.02% paclitaxel and the needles and roots of T. media Hicksii shrubs contain between about 0.005% to about 0.1% paclitaxel.
Therefore, it is of great interest to develop efficient methods of extracting high purity paclitaxel from plant material. The present invention provides methods for extracting high purity paclitaxel from plant material using chromatography followed by crystallization of the paclitaxel.